Anti-MST1 (aa 150-465) polyclonal antibody

Although cytokine-based therapy is a promising tool to control the progression of esophageal cancer, low therapeutic responses largely compromise treatment efficacy through unidentified mechanisms. The goal of our study was to explore the roles of macrophage stimulating 1 (Mst1) and mitophagy in enhancing IL-24-based cytokine therapy in esophageal cancer. Our data demonstrated that IL-24 application promoted cancer death by inducing mitochondrial stress, as manifested by mitochondrial ROS overproduction, mitochondrial potential dissipation, cellular ATP deprivation and mitochondrial death activation. Overexpression of Mst1 enhanced IL-24-mediated mitochondrial damage and further augmented IL-24-induced death in esophageal cancer. Molecular investigations illustrated that the IL-24-activated mitochondrial response is accompanied by activation of mitophagy, a protective mechanism to attenuate mitochondrial damage. However, Mst1 overexpression inhibited mitophagy activity, which was achieved by inactivating the ERK-Mfn2 signaling pathway. The reactivation of mitophagy abolished the cancer-killing effects of Mst1 overexpression on esophageal cancer. Altogether, our data demonstrate that IL-24-related therapeutic resistance is associated with mitophagy activation. Mst1 overexpression inhibits mitophagy activity via suppressing the ERK-Mfn2 pathway, ultimately augmenting IL-24-inducd esophageal cancer death via enhanced mitochondrial stress.

Neuronal cell death following traumatic brain injury (TBI) is a considerable contributor to neurological deficits. In our work, we explored the functions of Mammalian STE20-like kinase-1 (Mstl), a apoptosis-promoting kinase and also a pivotal bridgebuilder of apoptotic signaling, in the etiopathogenesis of an experimental rat model of TBI. We found that the phosphorylation level of Mst1 in injured area was significantly increased after TBI. Furthermore, we discovered that inhibition of Mst1 phosphorylation can effectively reduce neuronal cell death by inhibiting the activation of caspase 3 and suppressing the damage of DNA during TBI. In addition, the decreased of Mst1 phosphorylation level, not only reduced brain edema and blood-brain barrier (BBB) damage in injured region but also weakened the impairment of neurologic behavior during TBI. In conclusion, our work demonstrates that Mstl plays an important role in TBI-induced neuronal cell death, suggesting that Mstl is expected to be a potential therapeutic target for TBI. (C) 2017 Published by Elsevier B.V.